Salvage radiation therapy after radical prostatectomy

Posted by samadhi @samadhi, Jun 15 8:13am

Hello:
I had radical prostatectomy in 2020 but now PSA is high at 0.26 so radiation specialist recommended salvage radiation to prostate bed.

Can you share your experience with Salvage Radiation? Side effects to
1. Bladder
2. Bowel
3. Sexual function.

Thank you

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@consultant

You could do a PSMA at a PSA of 1.0 and studies show it is 60% sensitive. The likelihood you would have detectable metastatic disease at the low of level is very low. But, if any out of pocket cost to you is not a big issue, it can't hurt. 60% isn't 0% so it could be valuable if something lit up in your pelvis (most likely a lymph node), I would definitely opt for Whole Pelvic Salvage Radiation instead of just prostate bed. I'm sure most doctors just want more info and not more money but 0.2% vs 1%+ the scan is not going to find anything outside the prostate bed. I believe in past years some Urologists didn't recommend salvage treatment until something showed up on a scan. This has completely changed. If you are doing whole pelvic I'm not sure why they would do a PSMA PET if you are < 1.0 PSA unless they would do additional targeted radiation if in the unlikely chance they found any spots outside the prostate bed. It seems the whole pelvic would cover the entire area where it would most likely detect something?

My understanding is yes, your salvage treatment is your 2nd and final chance to eradicate the cancer completely. It's a matter of data combined with expert advice combined with personal preference on how aggressive you want to be with your salvage treatment. Some may be very wary of potential lifelong urinary issues going aggressive when they don't have "bad" post surgical pathology and/or are older and may die from something else. Others may want to risk increased side effects to try to increase the likelihood salvage therapy is curative. It's a tough decision. Because of my young age I believe it's wise to lean towards the modestly more aggressive route.

At 53 years old I had a PSA of 31. Negative bone scan. Negative PSMA scan for cancer outside the prostate. 3+4 Gleason score with 20% grade 4. Cribriform (small) morphology (most Urologists won't even look for this even though it's a risk factor for recurrence), tumor was "medium" size (between small/medium/large) according to my Urologist.

I had robotic surgery by the Chief or Urology at University of Washington/Fred Hutchinson Cancer Care in Seattle. It was 90% nerve sparing even though other Urologists recommended unilateral nerve sparing as the tumor was mostly on one side. My surgeon said he'd make the decision during surgery. He's done over 1,000 of them. My post surgery pathology was good. No positive surgical margins (he got the whole tumor), no seminal vesicle invasion, no extracapsular extension. I did have perineal invasion which is a relatively lower risk factor for recurrence than the other things like positive margins. I did also get extended lymph node removal, think it was 12-15 lymph nodes in my pelvis. None of them had cancer. 90% of nerves spared - my urinary function was 95% back to normal a year later, 80% back to normal 6 months later, Erectile function is about 80% normal, I can get erections but hard to maintain them during sex. A 5mg dose of Cialis makes me as good as I was before surgery (if not a little better lol.)

I had undetectable PSA (< 0.02) for 18 months and it hit 0.02 a year ago. My last PSA was checked at about my 2 year point a little over 4 months ago and it was still 0.02. I have my next one next week (stressful). I am expecting it to be higher but fingers crossed (this is because 0.02 usually is 90% confirmation of BCR but centers use two successive at 0.03 or above as confirmation just to be sure as to not risk overtreatment.) My Urologist said at this rate if it keeps going up it could be 10 years before I reach 0.2. But I will get salvage scheduled as soon as I hit 0.05 or higher. University of Washington doesn't recommend salvage until 0.2. And as I mentioned my Radiologist who I consulted with all along the way when making treatment decisions said no problem waiting until 0.1. I am of the opinion the longer after confirmed BCR you wait the more time for micrometastases to migrate outside the prostate bed. There are no studies that back up any benefit of doing salvage at that low of a level but if I'm only doing prostate bed, being fully healed from the surgery, the only benefit to waiting would be having another couple years maybe of not having a small set back in urinary and erectile function from the radiation.

I will forego ADT with salvage radiation for a couple reasons. Studies have shown it has no to very little significant benefit for people with favorable post surgical pathologies like me and very slow PSA rise. My initial PSA of 31 does technically put me in the "high risk" group but the post surfical pathology findings add a lot more clarity as to your situation. The high initial PSA meant I'd probably have a recurrence but my post surgery pathology means I have a high chance of the salvage radiation being curative with no evidence of cancer on the margins of the removed tissue or in the lymph nodes. The other reason I would forego ADT is I believe personally it starts the cancer on a path of morphing to no longer being androgen sensitive. So I will save the ADT until much later if salvage therapy fails to buy me time in hopes of future more successful treatments being developed.

While I would forego Lupron or Orgovyx or Bicalutamide (forgive spelling errors) during salvage therapy, I am curious about maybe doing a short course of Xtandi during salvage as it has shown even by itself to be more effective than those other drugs. Unfortunately I wouldn't qualify for insurance coverage unless my PSA DT was < 9 months which it looks like it won't be but it could accelerate. Until recently Xtandi was really only used much later in the cancer progression.

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I had Salvage Treatment to the WPRT and pelvic lymph nodes together with a short-term of ADT Feb - June 2023; substantially similar to ARM 3 of the SPPORT trial.
My uPSA results since have been < .02, undetectable, with the (dreaded) next 3 mo test next week.
The ADT Orgovyx was not pleasant, however my RO strongly recommended it for the statistical result benefit.
Surgery at age 72 in Aug 2022 confirmed Gleason 9, and postop pathology identified EPE, although I had clean surgical margins, lymph nodes and seminal vesicles. Postop PSA was .19, so my PSA was "persistent" postop, and I promptly followed up with salvage treatment.
2 friends had similar tx with 6 mos ADT.
All 3 of us at Johns Hopkins.
Clearly my hope and prayers are that the salvage treatment effectively killed the escaped PCa cells and that I will have years of freedom from progression. Of course, only time will tell.
Best wishes for you and your treatment decisions.

REPLY
@michaelcharles

I had Salvage Treatment to the WPRT and pelvic lymph nodes together with a short-term of ADT Feb - June 2023; substantially similar to ARM 3 of the SPPORT trial.
My uPSA results since have been < .02, undetectable, with the (dreaded) next 3 mo test next week.
The ADT Orgovyx was not pleasant, however my RO strongly recommended it for the statistical result benefit.
Surgery at age 72 in Aug 2022 confirmed Gleason 9, and postop pathology identified EPE, although I had clean surgical margins, lymph nodes and seminal vesicles. Postop PSA was .19, so my PSA was "persistent" postop, and I promptly followed up with salvage treatment.
2 friends had similar tx with 6 mos ADT.
All 3 of us at Johns Hopkins.
Clearly my hope and prayers are that the salvage treatment effectively killed the escaped PCa cells and that I will have years of freedom from progression. Of course, only time will tell.
Best wishes for you and your treatment decisions.

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Wish you all the best and freedom from progression.
May I ask how did you find Salvage radiation therapy? Did you have any side effects?
Best Regards

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@samadhi

Wish you all the best and freedom from progression.
May I ask how did you find Salvage radiation therapy? Did you have any side effects?
Best Regards

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My radiation treatments were 37 sessions over almost 8 weeks; primary side effects diarrhea and anal discomfort/pain beginning about 4 weeks into treatment. Resolved completely about 2 weeks following completion of radiation.
My 2 friends seemed to have had similar experiences. I do not think that I have any discernable radiation side effects since treatments ended + 2 weeks.
The Orgovyx side effects were not pleasant, but mild to moderate. And substantially dissipated 4 - 6 mos after last pill.
Hope this is helpful; best wishes.

REPLY
@michaelcharles

I had Salvage Treatment to the WPRT and pelvic lymph nodes together with a short-term of ADT Feb - June 2023; substantially similar to ARM 3 of the SPPORT trial.
My uPSA results since have been < .02, undetectable, with the (dreaded) next 3 mo test next week.
The ADT Orgovyx was not pleasant, however my RO strongly recommended it for the statistical result benefit.
Surgery at age 72 in Aug 2022 confirmed Gleason 9, and postop pathology identified EPE, although I had clean surgical margins, lymph nodes and seminal vesicles. Postop PSA was .19, so my PSA was "persistent" postop, and I promptly followed up with salvage treatment.
2 friends had similar tx with 6 mos ADT.
All 3 of us at Johns Hopkins.
Clearly my hope and prayers are that the salvage treatment effectively killed the escaped PCa cells and that I will have years of freedom from progression. Of course, only time will tell.
Best wishes for you and your treatment decisions.

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Sounds like you made the best decisions possible. With Gleason 9, EPE and persistent PSA, ADT + WPRT is definitely a wise decisions. John Hopkins is an excellent center, you were in good hands. Having clean lymph nodes post op definitely increases your chances your salvage treatment was successful.

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Sam - OK you have had a PSMA-Pet and its clear , what does it say in the pelvic area ? I had 22 sessions of Salvage /EBRT . Non chemicals or ADT . That was done at 0.14 . RO said you will likely need it , but only 22 sessions not 33-35 , as you case is like . He was 90% certain PSA was generated from Pelvic area . No Pet scan , just pelvic radiation. 2 year later im from 0.14 to now 0.041/0.040 . getting down there . The last 4 PSA tests have been down . Bladder and Bowel were jumpy for the first 3-5 months , and PSA didnt come down really much for 5-8 months ....then my body repaired . No issues will anything now . Hopeful PSA remains low . Dr's seem to think so . They terminated me at Victoria Cancer Clinic , and told me to get a referral from my URO or GP if PSA rises about 0.10 again ....but they feel it will stay down . I said OK . I was 58 at time of surgery and 59 at time of 22 sessions of salvage radiation . Salvage worked for me . Your PSA is not too bad , discuss maybe 22-25 sessions with RO , you may not need 35 . I find some of my buddy who got 30-38 sessions have more problems and take longer to heal . Avoid ADT , if possible . Let me know about the pelvic PSMA PET , as things could be different. When they peel back the Prostate from bladder I know URO's say they leave some cells behind . in fact , your PSA cell reading COULD be from perfectly normal cells dividing like they do . PC cell division is usually more rapid and invasive . What has you PSA profile and velocity been ? Gleason 3+4 or G 4+4 ? . Let me know a little about yoru pathology after operation. I hoped they saved your prostate - they save them here on Vancouver Island ....infact they redid my pathology just last month - I dont have a clue shy , nor does my RO I was talking to . He thinks it was done for accuracy ( they pull 15 per 100 at times ) to re look at cell types , breaches, and other feature . Mine was done accurate they say . Very little change from original pathology . Its good of Government insurance does this , they are called "Island Health " . I noticed they got a new robotics machine ( fancy one) . We are still waiting for a PSMA-PET scan . They say they can do them at Victoria Hospital but they need that particular radiation to give you a shot . I dotn know why they dont do them there as Canada is full of Uranium (2nd largest deposit in world ) and of course oil and Nat Gas (3rd largest light oil deposits in world ) ! The Uranium is used world wide for military, medical, and cars etc . I own 15% of small uranium producer , we sell all our Uranium to Cameco ( mine and labs ) who in turn sells it to Health clinics in Canada and USA and World , and hospitals after isolating certain elements for purpose .Geee I got off topic - sorry about that . Brother, your in my prayers, keep well. Let me know on the other stuff ! James on Vancouver Island .

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@heavyphil

I hear everything you’re saying and you sound EXACTLY like me as I watched my post surgical PSA slowly climb from 0.0 to .18 5 years post-op.
I badgered, cajoled and begged to start salvage treatment at .1. It’s obviously going UP, what are we waiting for??!! All the docs said NO; it could even be a few normal cells left over
from the nerve sparing surgery that were contributing PSA.
I was terrified by the idea of metastases occurring while the experts watched.
My RO at Sloan laughed out loud when I told him I WANTED the hormones. “I have to fight with men to get them to take them - they make all the difference!” But I knew I was down to my last at bat with this thing; if I didn’t kill it NOW, it was a lifetime of Xtandi or other really powerful, life altering drugs. I was placed on a 6 month course of Orgovyx combined with 25 salvage treatment of radiation - less than the usual 39 but at a higher dose for each.
The Orgovyx has not been a problem at all; side effects, but tolerable. PSA dropped to < .05 and T went from 610 to 5…in one month! Now in my second week of radiation.
I was 64 at diagnosis, Gleason4+3 with perineural invasion. Surgical pathology clean except for small break in capsule, which, my surgeon said was not significant since margins were negative.
I totally understand your aggressive stance given your age, etc. BUT, I don’t understand why you would forego a 6 month round of Orgovyx when it DOES weaken cancer cells significantly and makes them more vulnerable to the killing effects of radiation. If your Decipher score was low you probably DO NOT need them, but don’t know if you had this test. I did not over 5 yrs ago so I am taking no chances.
All the best in whatever course you take.
Phil

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I was more pro ADT until I really did a deep dive into it. There are multiple studies for Gleason 3+4 with slow PSA DT and favorable post surgical pathology, it has no significant effect on PCSM (Prostate Cancer Specific Mortality).

However I may fork out for a ArteraAI genomic test. It's newer and gives better data than Decipher. My Radiologist at UCLA actually said if I could afford it, it would be additional data to make a more informed decision. The results could tip the scale on my posture on ADT. With Orovyx it bring T down much more quickly than the other drugs and T comes back more quickly. I heard lots of exercise and some supplements can help a little with reducing side effects and even some do a low dose estradiol patch if SEs are very bad - it can vary from person to person. Still, if statistically there's no significant benefit for MY particular situation, I'd rather "save that bullet" should salvage fail and not give the cancer a jump start on the eventual progression to being androgen insensitive. Here's just a couple of the many studies that confirm ADT has ot long-term benefit when not having high risk pathology and doing salvage at very low PSA level.

Meta analysis of several studies, concluding it's beneficial only with high risk factors and when being treated a higher PSA levels (they probably had persistent PSA).
https://www.frontierspartnerships.org/journals/oncology-reviews/articles/10.3389/or.2023.10676/full
"A subgroup analyses revealed that the greatest benefit from the addition of ADT was observed in patients with pre-SRT PSA levels >0.7 ng/mL, GS 8–10, and PSM [16]. The French GETUG-AFU 16 trial compared the effect of the addition of short-term ADT with gosereline for 6 months to the SRT therapy (66 Gy) in 743 patients with high-risk factors for relapse and pre-SRT PSA of 0.2–2 ng/mL after RP. In that study, no statistically significant benefit for overall survival was demonstrated"
https://www.redjournal.org/article/S0360-3016(18)31032-0/pdf
"One of the most notable findings from RTOG 9601 was
that pre-SRT PSA was not only prognostic, it was predictive
of benefit from hormone therapy. The interaction test was
significant, which means that patients with lower pre-SRT
PSA are less likely to intrinsically benefit from hormone
therapy, in both a lower absolute benefit (decreased overall
survival by 4.1% from adding bicalutamide for pre-SRT
PSA of < 0.7 vs 24.6% overall survival improvement
from adding bicalutamide when PSA >1.5 ng/mL) and in a
relative sense as well (hazard ratio of 1.13 vs 0.45 for PSA
< 0.7 vs >1.5 ng/mL, respectively). This is in contrast to
other adverse features, such as higher Gleason score, which
did not predict which men will benefit most from the
addition of hormone therapy.
Similarly, GETUG-AFU-16, a trial predominately of
patients receiving early SRT, failed to show an improve
ment in development of metastasis or overall survival and
has thus not shown clinically meaningful benefit for these
patients from the addition of 6 months of a gonadotropin
releasing hormone (GnRH) agonist (2, 5). "

REPLY
@consultant

I was more pro ADT until I really did a deep dive into it. There are multiple studies for Gleason 3+4 with slow PSA DT and favorable post surgical pathology, it has no significant effect on PCSM (Prostate Cancer Specific Mortality).

However I may fork out for a ArteraAI genomic test. It's newer and gives better data than Decipher. My Radiologist at UCLA actually said if I could afford it, it would be additional data to make a more informed decision. The results could tip the scale on my posture on ADT. With Orovyx it bring T down much more quickly than the other drugs and T comes back more quickly. I heard lots of exercise and some supplements can help a little with reducing side effects and even some do a low dose estradiol patch if SEs are very bad - it can vary from person to person. Still, if statistically there's no significant benefit for MY particular situation, I'd rather "save that bullet" should salvage fail and not give the cancer a jump start on the eventual progression to being androgen insensitive. Here's just a couple of the many studies that confirm ADT has ot long-term benefit when not having high risk pathology and doing salvage at very low PSA level.

Meta analysis of several studies, concluding it's beneficial only with high risk factors and when being treated a higher PSA levels (they probably had persistent PSA).
https://www.frontierspartnerships.org/journals/oncology-reviews/articles/10.3389/or.2023.10676/full
"A subgroup analyses revealed that the greatest benefit from the addition of ADT was observed in patients with pre-SRT PSA levels >0.7 ng/mL, GS 8–10, and PSM [16]. The French GETUG-AFU 16 trial compared the effect of the addition of short-term ADT with gosereline for 6 months to the SRT therapy (66 Gy) in 743 patients with high-risk factors for relapse and pre-SRT PSA of 0.2–2 ng/mL after RP. In that study, no statistically significant benefit for overall survival was demonstrated"
https://www.redjournal.org/article/S0360-3016(18)31032-0/pdf
"One of the most notable findings from RTOG 9601 was
that pre-SRT PSA was not only prognostic, it was predictive
of benefit from hormone therapy. The interaction test was
significant, which means that patients with lower pre-SRT
PSA are less likely to intrinsically benefit from hormone
therapy, in both a lower absolute benefit (decreased overall
survival by 4.1% from adding bicalutamide for pre-SRT
PSA of < 0.7 vs 24.6% overall survival improvement
from adding bicalutamide when PSA >1.5 ng/mL) and in a
relative sense as well (hazard ratio of 1.13 vs 0.45 for PSA
< 0.7 vs >1.5 ng/mL, respectively). This is in contrast to
other adverse features, such as higher Gleason score, which
did not predict which men will benefit most from the
addition of hormone therapy.
Similarly, GETUG-AFU-16, a trial predominately of
patients receiving early SRT, failed to show an improve
ment in development of metastasis or overall survival and
has thus not shown clinically meaningful benefit for these
patients from the addition of 6 months of a gonadotropin
releasing hormone (GnRH) agonist (2, 5). "

Jump to this post

I’ve read these studies and, in fact, 2 Docs I consulted with said NO hormones if less than .7, which my .18 was.
However, my surgeon - a superstar in the field, on TV and used by the ‘bigshots’ failed to remove an adequate number of lymph nodes. He only did the first and closest one (the ‘bullseye’?) on each side. It was negative but far from to 6-9 on each side most recommend.
Ergo my RO team is taking no chances in attacking whatever is left. Also, the PSA velocity was increasing over time so something was gaining strength, right?
One thing I’ve learned on my road and in my reading is that this disease is totally unpredictable - you can bank on nothing and NEVER, EVER rest easy!

REPLY
@heavyphil

I hear everything you’re saying and you sound EXACTLY like me as I watched my post surgical PSA slowly climb from 0.0 to .18 5 years post-op.
I badgered, cajoled and begged to start salvage treatment at .1. It’s obviously going UP, what are we waiting for??!! All the docs said NO; it could even be a few normal cells left over
from the nerve sparing surgery that were contributing PSA.
I was terrified by the idea of metastases occurring while the experts watched.
My RO at Sloan laughed out loud when I told him I WANTED the hormones. “I have to fight with men to get them to take them - they make all the difference!” But I knew I was down to my last at bat with this thing; if I didn’t kill it NOW, it was a lifetime of Xtandi or other really powerful, life altering drugs. I was placed on a 6 month course of Orgovyx combined with 25 salvage treatment of radiation - less than the usual 39 but at a higher dose for each.
The Orgovyx has not been a problem at all; side effects, but tolerable. PSA dropped to < .05 and T went from 610 to 5…in one month! Now in my second week of radiation.
I was 64 at diagnosis, Gleason4+3 with perineural invasion. Surgical pathology clean except for small break in capsule, which, my surgeon said was not significant since margins were negative.
I totally understand your aggressive stance given your age, etc. BUT, I don’t understand why you would forego a 6 month round of Orgovyx when it DOES weaken cancer cells significantly and makes them more vulnerable to the killing effects of radiation. If your Decipher score was low you probably DO NOT need them, but don’t know if you had this test. I did not over 5 yrs ago so I am taking no chances.
All the best in whatever course you take.
Phil

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I am looking at having a PSMA Pet scan in a week. I was initially diagnosed with Gleason 3+4 two years ago but before having surgery my PSA was increasing from 6 to a 13. Got another opinion at UCLA, a second biopsy showed I was now Gleason 9. Prostectomy in July. PSA came back quickly after first 3 months. Had a PMA pet scan before I reached one. 1.0 which was negative. I then underwent 39 treatments of radiation in the prostate bed and six months of Lupron. I was below .04 after the treatment for only a couple of months now the PSA is at .6.
This entire time my doubling rate is frighteningly quick. My PSA is low but doubling every month now at .6. Of course I will do a PSMA Pet scan even though it may not show anything yet. What I read tells me my prospects are not great because of the velocity , yet my PSA is still low. I have not seen any recent studies showing the impact of PSMA with early ability to locate where this thing is. Dr. Sholz seems to believe it is a game changer. I sure hope so. Any advice would be greatly appreciated.

REPLY
@cooper1076

I am looking at having a PSMA Pet scan in a week. I was initially diagnosed with Gleason 3+4 two years ago but before having surgery my PSA was increasing from 6 to a 13. Got another opinion at UCLA, a second biopsy showed I was now Gleason 9. Prostectomy in July. PSA came back quickly after first 3 months. Had a PMA pet scan before I reached one. 1.0 which was negative. I then underwent 39 treatments of radiation in the prostate bed and six months of Lupron. I was below .04 after the treatment for only a couple of months now the PSA is at .6.
This entire time my doubling rate is frighteningly quick. My PSA is low but doubling every month now at .6. Of course I will do a PSMA Pet scan even though it may not show anything yet. What I read tells me my prospects are not great because of the velocity , yet my PSA is still low. I have not seen any recent studies showing the impact of PSMA with early ability to locate where this thing is. Dr. Sholz seems to believe it is a game changer. I sure hope so. Any advice would be greatly appreciated.

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So sorry to hear of this; you would have thought you’d be done with this by now….
I am not qualified to give you any clear advice as to how to proceed forward but I do see the dilemma: Wait for the PSA to increase to the point of becoming visible on PSMA - or go back on ADT to slow it down but by doing so you may NEVER visualize it on a scan. The first scenario is chancy because it could metastasize or spread further….the second puts you on ADT, possibly for life. What do your DRS say?

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@heavyphil

So sorry to hear of this; you would have thought you’d be done with this by now….
I am not qualified to give you any clear advice as to how to proceed forward but I do see the dilemma: Wait for the PSA to increase to the point of becoming visible on PSMA - or go back on ADT to slow it down but by doing so you may NEVER visualize it on a scan. The first scenario is chancy because it could metastasize or spread further….the second puts you on ADT, possibly for life. What do your DRS say?

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Waiting for the PSMA…

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